Genetics最新文献

{"title":"Evidence for a hydrogen sulfide-sensing E3 ligase in yeast.","authors":"Zane Johnson, Yun Wang, Benjamin M Sutter, Benjamin P Tu","doi":"10.1093/genetics/iyae154","DOIUrl":"10.1093/genetics/iyae154","url":null,"abstract":"<p><p>In yeast, control of sulfur amino acid metabolism relies upon Met4, a transcription factor that activates the expression of a network of enzymes responsible for the biosynthesis of cysteine and methionine. In times of sulfur abundance, the activity of Met4 is repressed via ubiquitination by the SCFMet30 E3 ubiquitin ligase, but the mechanism by which the F-box protein Met30 senses sulfur status to tune its E3 ligase activity remains unresolved. Herein, we show that Met30 responds to flux through the trans-sulfuration pathway to regulate the MET gene transcriptional program. In particular, Met30 is responsive to the biological gas hydrogen sulfide, which is sufficient to induce ubiquitination of Met4 in vivo. Additionally, we identify important cysteine residues in Met30's WD-40 repeat region that sense the availability of sulfur in the cell. Our findings reveal how SCFMet30 dynamically senses the flow of sulfur metabolites through the trans-sulfuration pathway to regulate the synthesis of these special amino acids.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population size rescaling significantly biases outcomes of forward-in-time population genetic simulations.","authors":"Amjad Dabi, Daniel R Schrider","doi":"10.1093/genetics/iyae180","DOIUrl":"10.1093/genetics/iyae180","url":null,"abstract":"<p><p>Simulations are an essential tool in all areas of population genetic research, used in tasks such as the validation of theoretical analysis and the study of complex evolutionary models. Forward-in-time simulations are especially flexible, allowing for various types of natural selection, complex genetic architectures, and non-Wright-Fisher dynamics. However, their intense computational requirements can be prohibitive to simulating large populations and genomes. A popular method to alleviate this burden is to scale down the population size by some scaling factor while scaling up the mutation rate, selection coefficients, and recombination rate by the same factor. However, this rescaling approach may in some cases bias simulation results. To investigate the manner and degree to which rescaling impacts simulation outcomes, we carried out simulations with different demographic histories and distributions of fitness effects using several values of the rescaling factor, Ǫ, and compared the deviation of key outcomes (fixation times, allele frequencies, linkage disequilibrium, and the fraction of mutations that fix during the simulation) between the scaled and unscaled simulations. Our results indicate that scaling introduces substantial biases to each of these measured outcomes, even at small values of Ʈ. Moreover, the nature of these effects depends on the evolutionary model and scaling factor being examined. While increasing the scaling factor tends to increase the observed biases, this relationship is not always straightforward, thus it may be difficult to know the impact of scaling on simulation outcomes a priori. However, it appears that for most models, only a small number of replicates was needed to accurately quantify the bias produced by rescaling for a given Ʈ. In summary, while rescaling forward-in-time simulations may be necessary in many cases, researchers should be aware of the rescaling procedure's impact on simulation outcomes and consider investigating its magnitude in smaller scale simulations of the desired model(s) before selecting an appropriate value of Ʈ.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defects in the central metabolism prevent thymineless death in Escherichia coli, while still allowing significant protein synthesis.","authors":"Sharik R Khan, Andrei Kuzminov","doi":"10.1093/genetics/iyae142","DOIUrl":"10.1093/genetics/iyae142","url":null,"abstract":"<p><p>Starvation of Escherichia coli thyA auxotrophs for the required thymine or thymidine leads to the cessation of DNA synthesis and, unexpectedly, to thymineless death (TLD). Previously, TLD-alleviating defects were identified by the candidate gene approach, for their contribution to replication initiation, fork repair, or SOS induction. However, no TLD-blocking mutations were ever found, suggesting a multifactorial nature of TLD. Since (until recently) no unbiased isolation of TLD suppressors was reported, we used enrichment after insertional mutagenesis to systematically isolate TLD suppressors. Our approach was validated by isolation of known TLD-alleviating mutants in recombinational repair. At the same time, and unexpectedly for the current TLD models, most of the isolated suppressors affected general metabolism, while the strongest suppressors impacted the central metabolism. Several temperature-sensitive (Ts) mutants in important/essential functions, like nadA, ribB, or coaA, almost completely suppressed TLD at 42°C. Since blocking protein synthesis completely by chloramphenicol prevents TLD, while reducing protein synthesis to 10% alleviates TLD only slightly, we measured the level of protein synthesis in these mutants at 42°C and found it to be 20-70% of the WT, not enough reduction to explain TLD prevention. We conclude that the isolated central metabolism mutants prevent TLD by affecting specific TLD-promoting functions.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linkage equilibrium between rare mutations.","authors":"Anastasia S Lyulina, Zhiru Liu, Benjamin H Good","doi":"10.1093/genetics/iyae145","DOIUrl":"10.1093/genetics/iyae145","url":null,"abstract":"<p><p>Recombination breaks down genetic linkage by reshuffling existing variants onto new genetic backgrounds. These dynamics are traditionally quantified by examining the correlations between alleles, and how they decay as a function of the recombination rate. However, the magnitudes of these correlations are strongly influenced by other evolutionary forces like natural selection and genetic drift, making it difficult to tease out the effects of recombination. Here, we introduce a theoretical framework for analyzing an alternative family of statistics that measure the homoplasy produced by recombination. We derive analytical expressions that predict how these statistics depend on the rates of recombination and recurrent mutation, the strength of negative selection and genetic drift, and the present-day frequencies of the mutant alleles. We find that the degree of homoplasy can strongly depend on this frequency scale, which reflects the underlying timescales over which these mutations occurred. We show how these scaling properties can be used to isolate the effects of recombination and discuss their implications for the rates of horizontal gene transfer in bacteria.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting the role of the spindle assembly checkpoint in the formation of gross chromosomal rearrangements in Saccharomyces cerevisiae.","authors":"Yue Yao, Ziqing Yin, Fernando R Rosas Bringas, Jonathan Boudeman, Daniele Novarina, Michael Chang","doi":"10.1093/genetics/iyae150","DOIUrl":"10.1093/genetics/iyae150","url":null,"abstract":"<p><p>Multiple pathways are known to suppress the formation of gross chromosomal rearrangements (GCRs), which can cause human diseases including cancer. In contrast, much less is known about pathways that promote their formation. The spindle assembly checkpoint (SAC), which ensures the proper separation of chromosomes during mitosis, has been reported to promote GCR, possibly by delaying mitosis to allow GCR-inducing DNA repair to occur. Here, we show that this conclusion is the result of an experimental artifact arising from the synthetic lethality caused by the disruption of the SAC and loss of the CIN8 gene, which is often lost in the genetic assay used to select for GCRs. After correcting for this artifact, we find no role of the SAC in promoting GCR.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic background affects the strength of crossover interference in house mice.","authors":"Andrew P Morgan, Bret A Payseur","doi":"10.1093/genetics/iyae146","DOIUrl":"10.1093/genetics/iyae146","url":null,"abstract":"<p><p>Meiotic recombination is required for faithful chromosome segregation in most sexually reproducing organisms and shapes the distribution of genetic variation in populations. Both the overall rate and the spatial distribution of crossovers vary within and between species. Adjacent crossovers on the same chromosome tend to be spaced more evenly than expected at random, a phenomenon known as crossover interference. Although interference has been observed in many taxa, the factors that influence the strength of interference are not well understood. We used house mice (Mus musculus), a well-established model system for understanding recombination, to study the effects of genetics and age on recombination rate and interference in the male germline. We analyzed crossover positions in 503 progeny from reciprocal F1 hybrids between inbred strains representing the three major subspecies of house mice. Consistent with previous studies, autosomal alleles from M. m. musculus tend to increase recombination rate, while inheriting a M. m. musculus X chromosome decreases recombination rate. Old males transmit an average of 0.6 more crossovers per meiosis (5.0%) than young males, though the effect varies across genetic backgrounds. We show that the strength of crossover interference depends on genotype, providing a rare demonstration that interference evolves over short timescales. Differences between reciprocal F1s suggest that X-linked factors modulate the strength of interference. Our findings motivate additional comparisons of interference among recently diverged species and further examination of the role of paternal age in determining the number and positioning of crossovers.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropeptide signaling network of Caenorhabditis elegans: from structure to behavior.","authors":"Jan Watteyne, Aleksandra Chudinova, Lidia Ripoll-Sánchez, William R Schafer, Isabel Beets","doi":"10.1093/genetics/iyae141","DOIUrl":"10.1093/genetics/iyae141","url":null,"abstract":"<p><p>Neuropeptides are abundant signaling molecules that control neuronal activity and behavior in all animals. Owing in part to its well-defined and compact nervous system, Caenorhabditis elegans has been one of the primary model organisms used to investigate how neuropeptide signaling networks are organized and how these neurochemicals regulate behavior. We here review recent work that has expanded our understanding of the neuropeptidergic signaling network in C. elegans by mapping the evolutionary conservation, the molecular expression, the receptor-ligand interactions, and the system-wide organization of neuropeptide pathways in the C. elegans nervous system. We also describe general insights into neuropeptidergic circuit motifs and the spatiotemporal range of peptidergic transmission that have emerged from in vivo studies on neuropeptide signaling. With efforts ongoing to chart peptide signaling networks in other organisms, the C. elegans neuropeptidergic connectome can serve as a prototype to further understand the organization and the signaling dynamics of these networks at organismal level.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sharp decline in male fertility in F2 hybrids of the female-heterogametic silk moth Bombyx.","authors":"Kana Matsukawa, Yasuko Kato, Aya Yoshida, Hisaka Onishi, Sachiko Nakano, Masanobu Itoh, Toshiyuki Takano-Shimizu-Kouno","doi":"10.1093/genetics/iyae149","DOIUrl":"10.1093/genetics/iyae149","url":null,"abstract":"<p><p>Sexual selection drives rapid evolution of morphological, physiological, and behavioral traits, especially in males, and it may also drive the rapid evolution of hybrid male sterility. Indeed, the faster male theory of speciation was once viewed as a major cause of Haldane's rule in male-heterogametic XY taxa, but is increasingly being replaced by the genetic conflict hypothesis partly because it cannot explain the faster evolution of hybrid female sterility in female-heterogametic ZW taxa. The theory nonetheless predicts that there should be more genes for hybrid male sterility than for hybrid female sterility even in such taxa, but this remains untested. Thus, finding evidence for the faster male theory of reproductive isolation beyond the F1 generation in ZW systems still represents a challenge to studying the impact of sexual selection. In this study, we examined F2 hybrids between the domesticated silkworm Bombyx mori and the wild silk moth Bombyx mandarina, which have ZW sex determination. We found that although only females showed reduced fertility in the F1 generation, the F2 hybrid males had a significant reduction in fertility compared with the parental and F1 males. Importantly, 27% of the F2 males and 15% of the F2 females were completely sterile, suggesting the presence of recessive incompatibilities causing male sterility in female-heterogametic taxa.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Life history in Caenorhabditis elegans: from molecular genetics to evolutionary ecology.","authors":"Christian Braendle, Annalise Paaby","doi":"10.1093/genetics/iyae151","DOIUrl":"10.1093/genetics/iyae151","url":null,"abstract":"<p><p>Life history is defined by traits that reflect key components of fitness, especially those relating to reproduction and survival. Research in life history seeks to unravel the relationships among these traits and understand how life history strategies evolve to maximize fitness. As such, life history research integrates the study of the genetic and developmental mechanisms underlying trait determination with the evolutionary and ecological context of Darwinian fitness. As a leading model organism for molecular and developmental genetics, Caenorhabditis elegans is unmatched in the characterization of life history-related processes, including developmental timing and plasticity, reproductive behaviors, sex determination, stress tolerance, and aging. Building on recent studies of natural populations and ecology, the combination of C. elegans' historical research strengths with new insights into trait variation now positions it as a uniquely valuable model for life history research. In this review, we summarize the contributions of C. elegans and related species to life history and its evolution. We begin by reviewing the key characteristics of C. elegans life history, with an emphasis on its distinctive reproductive strategies and notable life cycle plasticity. Next, we explore intraspecific variation in life history traits and its underlying genetic architecture. Finally, we provide an overview of how C. elegans has guided research on major life history transitions both within the genus Caenorhabditis and across the broader phylum Nematoda. While C. elegans is relatively new to life history research, significant progress has been made by leveraging its distinctive biological traits, establishing it as a highly cross-disciplinary system for life history studies.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of multimodal deep learning methods for genomic-enabled prediction in plant breeding.","authors":"Osval A Montesinos-López, Moises Chavira-Flores, Kiasmiantini, Leo Crespo-Herrera, Carolina Saint Piere, HuiHui Li, Roberto Fritsche-Neto, Khalid Al-Nowibet, Abelardo Montesinos-López, José Crossa","doi":"10.1093/genetics/iyae161","DOIUrl":"10.1093/genetics/iyae161","url":null,"abstract":"<p><p>Deep learning methods have been applied when working to enhance the prediction accuracy of traditional statistical methods in the field of plant breeding. Although deep learning seems to be a promising approach for genomic prediction, it has proven to have some limitations, since its conventional methods fail to leverage all available information. Multimodal deep learning methods aim to improve the predictive power of their unimodal counterparts by introducing several modalities (sources) of input information. In this review, we introduce some theoretical basic concepts of multimodal deep learning and provide a list of the most widely used neural network architectures in deep learning, as well as the available strategies to fuse data from different modalities. We mention some of the available computational resources for the practical implementation of multimodal deep learning problems. We finally performed a review of applications of multimodal deep learning to genomic selection in plant breeding and other related fields. We present a meta-picture of the practical performance of multimodal deep learning methods to highlight how these tools can help address complex problems in the field of plant breeding. We discussed some relevant considerations that researchers should keep in mind when applying multimodal deep learning methods. Multimodal deep learning holds significant potential for various fields, including genomic selection. While multimodal deep learning displays enhanced prediction capabilities over unimodal deep learning and other machine learning methods, it demands more computational resources. Multimodal deep learning effectively captures intermodal interactions, especially when integrating data from different sources. To apply multimodal deep learning in genomic selection, suitable architectures and fusion strategies must be chosen. It is relevant to keep in mind that multimodal deep learning, like unimodal deep learning, is a powerful tool but should be carefully applied. Given its predictive edge over traditional methods, multimodal deep learning is valuable in addressing challenges in plant breeding and food security amid a growing global population.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}